The ultimate goal of this research is to elucidate the mechanisms which operate at the transcriptional level to regulate RNA synthesis and how these parameters are altered as a function of age. The specific emphasis will be to determine the level of each DNA-dependent RNA polymerase in nuclei and mitochondria of mice at various biological ages and to correlate any observed change with that expected from measurement of the rate of RNA synthesis. Mitochondrial DNA will be examined for an age dependent accumulation of single strand cleavages. If a positive result is obtained, the levels of DNA repair and degradative enzymes in mitochondrial extracts will be determined. A search will also be made for factors which are required for specific initiation and termination of RNA synthesis. If regulatory factors are found, an age profile will be determined.